dbSNP rs4597022: HNRNPF:c.-52-1836G>C (chr10-43389772-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098204.2(HNRNPF):c.-52-1836G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,014 control chromosomes in the GnomAD database, including 10,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10766 hom., cov: 32)

Consequence

HNRNPF
NM_001098204.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

Publications

2 publications found

Variant links:

Genes affected

HNRNPF (HGNC:5039): (heterogeneous nuclear ribonucleoprotein F) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNAs which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

HNRNPF links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098204.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNRNPF	NM_001098204.2	MANE Select	c.-52-1836G>C	intron	N/A	NP_001091674.1	P52597
HNRNPF	NM_001098205.2		c.-52-1836G>C	intron	N/A	NP_001091675.1	P52597
HNRNPF	NM_001098206.2		c.-52-1836G>C	intron	N/A	NP_001091676.1	P52597

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNRNPF	ENST00000682386.1	MANE Select	c.-52-1836G>C	intron	N/A	ENSP00000507787.1	P52597
HNRNPF	ENST00000337970.7	TSL:1	c.-52-1836G>C	intron	N/A	ENSP00000338477.3	P52597
HNRNPF	ENST00000357065.8	TSL:1	c.-52-1836G>C	intron	N/A	ENSP00000349573.4	P52597

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52390

AN:

151896

Hom.:

10740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.345

AC:

52466

AN:

152014

Hom.:

10766

Cov.:

AF XY:

0.346

AC XY:

25671

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.585

AC:

24227

AN:

41438

American (AMR)

AF:

0.284

AC:

4346

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1234

AN:

3468

East Asian (EAS)

AF:

0.265

AC:

1373

AN:

5180

South Asian (SAS)

AF:

0.355

AC:

1705

AN:

4804

European-Finnish (FIN)

AF:

0.251

AC:

2653

AN:

10558

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.235

AC:

15981

AN:

67978

Other (OTH)

AF:

0.305

AC:

643

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1590

3179

4769

6358

7948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.297

Hom.:

1012

Bravo

AF:

0.357

Asia WGS

AF:

0.329

AC:

1144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.4

(source)

DANN

Benign

0.66

PhyloP100

-0.090

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over